It is planned to examine the possible rate limiting reactions in gluconeogenesis, ketogenesis and amino acid metabolism under various physiological states. These various states will be produced by the use of diets and/or hormones. The use of liver perfusion techniques will be used in conjunction with various substrates or combination of substrates to ascertain which reactions may be rate limiting under each of these conditions. The relationship of gluconeogenesis and ketogenesis will also be examined under these various conditions to see if this relationship, as occurs in starvation and diabetes, is correlated in many other states. The possibility of metabolic compartmentalization, in addition to sub-cellular organelle compartmentalization, in the liver will also be examined. Separation and the role of initiation and maintenance of "enzyme induction" will be examined by combining in vivo treatment with liver perfusion studies. The relationship of enzyme activity and metabolic potential under "optimal" conditions will also be examined in the perfused liver of animals treated various diets and/or hormones to determine if enzyme activity is limiting in the presence of excess substrate or whether other factors become important in a system as complex as the perfused liver.